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Killer Microbe

Classroom Activity

Activity Summary
Students model how horizontal gene transfer (e.g., conjugation) contributes to the spread of antibiotic resistance genes in bacteria.

Learning Objectives
Students will be able to:

• explain how bacterial cells can acquire new genes through conjugation.

• describe how a population of bacteria can evolve to become antibiotic resistant.

• use specific, real-world examples to show how quickly bacteria may develop resistance to new antibiotics.

• understand how rapidly bacteria reproduce, and discuss how this reproduction rate makes it possible for populations of bacteria to quickly adapt to new antibiotics.

Suggested Time
One class period

• Tracking the Spread of Antibiotic Resistance student handout (PDF)
• Brown paper lunch bags (one per student)
• Sheets of green and yellow construction paper (or other objects of uniform shape, size, and weight, such as poker chips—but be certain the objects you use come in two different colors)
• Scissors

Background
The discovery in the 1940s of the first antibiotics changed the course of human history. For the first time, people had the ability to fight bacterial infections, such as tuberculosis, that were once deadly. But resistance to those same life-saving drugs is one of the greatest challenges facing medicine today. The rise of antibiotic resistance over the past half-century is one of the most dramatic and compelling examples of evolution in action. Bacteria have adapted to nearly every antibiotic we've developed. Their ability to reproduce quickly and exchange bits of DNA enable bacteria to have this degree of adaptability.

Bacteria are single-celled prokaryotic organisms, which means that they lack a nucleus. Compared to eukaryotic organisms—organisms such as yeast and humans—which corral their DNA inside of the cell nucleus, bacterial DNA floats freely in the cytoplasm. Most often, this is in the form of a single, circular chromosome, though some bacterial strains have multiple circular chromosomes or occasionally linear chromosomes. Many bacterial cells also contain additional loops of DNA called plasmids. These structures carry genes in addition to the genes on the bacterial chromosome and can replicate independently of the chromosome. Plasmids often contain genes for antibiotic resistance.

Bacterial cells differ from human cells in their ability to manipulate and share their DNA. Bacteria of different species can exchange bits of DNA through a process called conjugation, in which one bacterium extends a tube-like projection to another and delivers a plasmid or plasmids to it. Conjugation is one form of a process called horizontal gene transfer, which is an exchange of genetic material by methods other than direct transmission from parents to offspring (which is called vertical gene transfer).

Researchers suggest horizontal gene transfer is one means by which previously harmless bacteria may acquire the genes that give them antibiotic resistance. In the case of A. baumannii, the bacteria featured in the NOVA scienceNOW segment Killer Microbe, recent analysis of its genome shows that it has picked up dozens of drug-resistance genes from other species such as E. coli and Salmonella. Given the rapid rate at which bacteria reproduce, it's easy to see how newly acquired genes—especially those that help bacteria fight the drugs meant to kill them—can quickly spread through a population.

In this activity, your students will model horizontal gene transfer to demonstrate how conjugation can introduce new genes throughout a bacterial population. As a follow-up, they will view an animation showing how quickly bacterial cells reproduce, and they'll make inferences about the spread of antibiotic resistance, whether acquired via mutation or horizontal gene transfer.

• Bookmark class computers with the Web pages Evolution of Antibiotic Resistance, Arms race with a superbug, and Infectious disease: bacterial conjugation
• Print enough copies of the Tracking the Spread of Antibiotic Resistance handout so that each student will have one.
• Cut the construction paper into 1" circles. Make a total of 5 yellow circles for every five students in the class, as well as 5 green circles for each student in the class minus five students. In other words, for a class of 25, you would make 25 yellow circles and 100 green circles (20 students would get 5 green circles each, for a total of 100). You also may use different-colored rubber bands, poker chips, or other round materials for the activity if these are readily available.
• Green circles represent plasmids that do not carry a gene for antibiotic resistance. Yellow circles represent plasmids that do carry a gene for antibiotic resistance.
• Prepare a paper lunch bag for each student. For every five students in the class, one bag should contain five yellow circles. The remaining bags should each contain five green circles. For a class of 25, you should have five bags containing yellow circles and 20 bags containing green circles.
• On an overhead or on the board, draw the table found on the student handout.

Remind students that the direct transfer of plasmids between bacterial cells can sometimes transfer genes for antibiotic resistance from one bacterium to another. The process is termed conjugation. For a quick review, show them the animation Infectious disease: bacterial conjugation.

1. Hand out the paper bags. Tell students to look inside their own bag, but not to tell other students what their bag contains. Explain that the bags represent individual bacterial cells, and that each bag contains paper circles that represent plasmids.

2. Explain that they will walk around the room simulating bacterial conjugation—each student will exchange circles by taking a circle from another student's bag without looking at it and then placing it in his or her own bag. They should do this until everyone has made five exchanges with different students.

3. After the five exchanges, have students count how many yellow circles they have in their bags. Indicate in the table the number of students with yellow circles, as well as the number of yellow circles per student. Have students write their answers in the second row, "After Round 1 Exchanges, " of the table on the handout.

4. Ask students to raise their hands if they started out with no yellow circles and then to lower their hands if they still have no yellow circles. Ask for a volunteer to describe the change that took place. At this point, you may reveal the number of students who started out with yellow circles.

5. Have students fill in this number on the first row of the table, under the column "Actual number of students with yellow circles." They also should fill in the number of students who started out without yellow circles before the Round 1 exchange. Ask for a volunteer to describe how these numbers changed after round 1.

6. Ask the class to predict how the number of students with yellow circles might change after the next round. Make sure students complete the first two rows of the table on the handout before they begin Round 2.

1. Have students repeat the exchange round once more (5 exchanges), and tally the number of students with and without yellow circles, as well as the number of yellow circles each student has.

2. Ask students to predict what will happen if the class is exposed to an antibiotic, and enter their predictions in the table. They should recognize that any students with yellow circles will "survive."

1. Have students repeat the exchange round once more (5 exchanges). This time, tell them they will simulate antibiotic exposure. Have students with no yellow circles sit out this round. Tally the number of students with and without yellow circles, as well as the number of yellow circles each student has.

2. Ask for a volunteer to explain why students without yellow circles sat out this round. You may need to review the role of antibiotic-resistance genes on the yellow "plasmids."

3. Raise the following points for discussion:

   • How many students have more than one yellow circle? More than two? Three or more?
   • Remind students that yellow circles represent plasmids carrying genes for antibiotic resistance. What would be an advantage to a bacterial cell of having more than one of these plasmids? Do students think plasmid number has any effect on a bacterium's ability to resist antibiotics?
   • Why do doctors tell people to take antibiotics for ten to fourteen days? Why not just one dose?

1. Show the animation Evolution of Antibiotic Resistance and then ask students to describe the animation's key points. The animation shows how a population of bacteria changes over time with repeated exposure to an antibiotic. You may need to prompt them by suggesting the rod-shaped structures are the bacteria E. coli and the wave that washes over the screen is an antibiotic such as streptomycin.

2. Ask students to list the main reasons why some bacteria died off in the animation, while others did not. Could there be other reasons? The bacteria that survived probably had a gene that gave them resistance to the antibiotic. Also, the antibiotic may not have come in contact with some of the cells if they were tightly packed.

3. Next, direct students to the interactive Arms race with a superbug. Alternatively, you may draw the table below on the board. NOTE: the "????" in the last row indicates that as of this writing, there have been no reports of tigecycline resistance. If the past provides any hints, however, it's only a matter of time before this antibiotic, too, loses its punch.

After students have viewed the chart or interactive, ask the following questions:

• How many of the seven antibiotics on this chart introduced since 1941 is the bacteria Staph aureus resistant to? Six

• With the exception of vancomycin, what is the average length of time from the first use of an antibiotic to the first reported resistance to it? 1.25 years

• Propose a possible mechanism by which Staph aureus became resistant to vancomycin. Through horizontal gene transfer, or conjugation with another kind of bacteria called Enteorcocci. Alternatively, a random mutation could have resulted in vancomycin resistance.

• Based on the information in this interactive and what students have already learned, what do they expect to happen with the newest class of antibiotics on the timeline? Answers may vary, but students should recognize that one day, bacteria will likely be able to resist these antibiotics as well.

As an extension, ask students if any of them have ever taken an antibiotic, such as penicillin, amoxicillin, or erythromycin. Then, ask them if they remember for how many days they had to take the medication. Ask them to research the following questions:

• How do antibiotics work?
• How do antibiotics get to the bacteria in the body?

ASSESSMENT
Student Handout Questions

1. In the activity, what do the yellow and green circles represent? Plasmids; yellow ones contain a gene for antibiotic resistance; green ones do not. The bag? Individual bacterial cells. Your arm and hand? The structures in a bacterium that transfer plasmids from one to the next.
2. How many bacteria were originally antibiotic resistant? Five How many bacteria were antibiotic resistant after the first two exchange rounds? The actual number will vary, but it should be greater than the original five.
3. What is the trend of antibiotic resistance as seen in this simulation? Antibiotic resistance increases with time and becomes an established characteristic in the population.
4. Evolution is sometimes defined as a change in gene frequency in a population over time. How does this activity model this definition of evolution? Answers may vary, as will numbers. A sample answer is: The activity began with 5 out of 25 students having a gene for antibiotic resistance. It ended with 17 out of 25 students having this gene. Because the frequency of the gene in this population changed over time, we have seen evolution take place.
5. Explain why some students had to sit out round 3. Round 3 introduced an antibiotic. Students who lacked the antibiotic-resistance gene on the yellow plasmid had to sit out this round because they did not survive exposure to the antibiotic.
6. How do you predict 'bacteria' with different numbers of yellow circles might react to repeated exposure to an antibiotic? Having more yellow circles gives them more copies of the resistance gene, and may help them resist additional exposure to the antibiotic.
7. If you have an infection and your doctor prescribes an antibiotic, why is it important to complete the full ten-to-fourteen day course of the medication, rather than to stop as soon as you start feeling better? Only by taking the full course can you be sure of killing all the bacteria in your system that caused you to become sick in the first place; if any of those bacteria remain, your infection could return. In addition, by not killing them, you've given them more time to reproduce, increasing the possibility that they may acquire resistance either from random mutations or from other bacteria in your system and become tougher to fight off next time you're sick.

Use the following rubric to assess each team's work.

The Iraqi Bacteria activity aligns with the following National Science Education Standards (see books.nap.edu/html/nses).

Grades 9-12
Life Science

• The cell
• Biological evolution

Science in Personal and Social Perspectives

• Personal and Community Health
• Natural and human-induced hazards

Classroom Activity Author

Jennifer Cutraro and WGBH Educational Outreach Staff, with contributions by Margy Kuntz.

Margy Kuntz has written and edited educational materials for more than 24 years. She has authored numerous educational supplements, basal text materials, and trade books on health, science, math, and computers.

Jennifer Cutraro has 12 years of experience in science writing and education. She has written text and ancillaries for Houghton Mifflin, K¹², and Delta Education and has taught science and environmental education at science centers across the country. She also contributes news and feature stories about science and health to media outlets including The Los Angeles Times, The Boston Globe, Science News for Kids and Scholastic Science World.